The use of keratin‐based wound products on refractory wounds

Keratin proteins have been shown to play a key role in wound healing. Controlled keratin gene (KRT) expression promotes cell growth, migration and differentiation, and as an example of the importance of keratin proteins, absence of KRT17 has been shown to delay wound closure. In addition, downregulation of KRT6 and KRT16 in non‐healing chronic venous ulcers suggests that deregulation of keratin expression contributes to non‐healing phenotype. A sample of 45 chronic wounds of mixed aetiologies presenting in 31 patients were treated with keratin‐based novel topical wound healing products. Thirty‐seven wounds or 82% of wounds were either healed or reduced in size of >50% during treatment, with 29 (64%) healing completely and an additional 8 wounds experiencing 50% wound size reduction or greater. Of the wounds that responded, 15 required antimicrobial treatment during their course of treatment, suggesting that keratin dressing treatment should be interrupted briefly and then restarted when wound infection occur.     

A change in the prevalence and the etiological factors of chronic wounds in Helsinki metropolitan area during 2008‐2016

The prevalence of chronic wounds in the Helsinki metropolitan area in 2008 was investigated. Thereafter, a specialised wound care team was founded as part of the City of Helsinki Health Services, aiming for early diagnoses of chronic wounds. In the current study, we have repeated the prevalence study to analyse the changes in the prevalence of chronic wounds. A questionnaire on wound patients was sent to all units of social and health care in the Helsinki metropolitan area. We asked about the number of patients with wounds treated during a 24‐hour period, as well the aetiology and location of the wounds. A total of 911 patients had, altogether, 1021 wounds. Thus, prevalence was 0.08%. Pressure and multifactorial ulcers were the most common aetiological groups, whereas wound without defined aetiology had diminished greatly (61%) The prevalence of chronic wound decreased when compared with 2008 (0.08% vs 0.1%). The number of elderly people aged over 65 years had increased 35%, and the age‐adjusted prevalence had decreased. Wounds are treated mostly in primary care units and as outpatients. Therefore, the following conclusion may be reached: diagnostic process and implementation of treatment paths are strengthened within primary care units, yet prevalence of wounds has decreased.     

Epidemiology of chronic wounds in Germany: Analysis of statutory health insurance data

Epidemiologic analyses in routine care of chronic wounds are scarce, and published studies show wide variations. This study analyzes the population‐based prevalence and incidence of chronic wounds in Germany. Secondary analyses of data from a German statutory health insurance with about 9 million insured persons were examined (2010 to 2012). Internal diagnostic validations were used to control for different inclusion criteria. In 2012, 1.04% (95% CI 1.03–1.05) of insured patients had a wound diagnosis, including 0.70% with leg ulcers and 0.27% with diabetic ulcers. Wound treatment was received by 0.43% (0.43–0.44) of patients. Prevalence and incidence increased over 3 years. Extrapolated to the German population, there were 786,407 prevalent and 196,602 incident chronic wounds, including 326,334/172,026 patients who underwent wound‐relevant treatment in 2012. There is an annually increasing frequency of chronic wounds in Germany. Chronic wound epidemiology is sensitive to wound treatment as a filter criterion.     

Prevalence of chronic wounds and structural quality indicators of chronic wound care in Dutch nursing homes

The aim of this study was to measure the prevalence of (infected) chronic wounds in Dutch nursing homes and to explore which signs and symptoms are used to diagnose infected chronic wounds. Moreover, it was to determine which structural quality indicators related to chronic wound care at ward and institutional levels were fulfilled. In April 2012, as part of the annual National Prevalence Measurement of Care Problems of Maastricht University [Landelijke Prevalentiemeting Zorgproblemen (LPZ)], a multi‐center cross‐sectional point‐prevalence measurement was carried out together with an assessment of relevant care quality indicators. The prevalence was 4·2%; 16 of 72 (22%) chronic wounds were considered to be infected. Increase of exudate (81·3%; n = 13), erythema (68·8%; n = 11), pain (56·3%; n = 9) and wound recalcitrance (56·3%; n = 9) were considered to be diagnostic signs and symptoms of a chronic wound infection. Although at institutional level most quality indicators were fulfilled, at ward level this was not the case. Despite the relatively low number of residents, we consider our population as representative for the nursing home population. It may be an advantage to appoint specific ward nurses and to provide them specifically with knowledge and skills concerning chronic wounds.     

Clinical experiences derived from implementation of an easy to use concept for treatment of wound healing by secondary intention and guidance in selection of appropriate dressings

The main objective of this case‐cohort‐type observational study conducted at different Surgical Departments of the Charité‐Universitätsmedizin in Berlin was to evaluate the sequential use concept first described by Systagenix Wound Management in 2007. Fifty‐two patients with different wound healing by secondary intention were treated for 7 weeks at the Charité‐Universitätsmedizin in Berlin. A multidisciplinary team worked together to reach consensus in wound assessment; in classification of infection status according to the criteria described by European Wound Management Association (EWMA); in treatment protocol and on dressings to be used to ‘cover’ wounds. Before dressing application, all wounds were cleaned from debris. Following the sequential use concept, wounds classified as stages 2 and 3 were dressed with SILVERCEL^® and TIELLE^® or TIELLE PLUS^® to ‘clean’ the wounds. After 2–3 weeks, treatment was changed to PROMOGRAN PRISMA^® and TIELLE^® to ‘close and cover’ wounds, thus providing optimal wound healing. Wounds classified as non infected were dressed with PROMOGRAN PRISMA^® and TIELLE^® during the complete treatment period. Patients were asked to evaluate the treatment using a simplified questionnaire developed at the Charité‐Universitätsmedizin in Berlin. Wounds comprised 37 surgical procedures, 8 chronic mixed ulcer, 4 pressure sores, 1 diabetic foot ulcer, 1 venous leg ulcer, and 1 mixed arterial/venous ulcer. At baseline, 12 wounds were classified as stage 3, 38 wounds as stage 2 and 2 wounds as stage 1. After 7 weeks of treatment, all patients showed a positive clinical response to the sequential use treatment. Results of wound size showed a high significant progression of wound healing expressed with a profound reduction of wound area (P in all measurements <0·001, chi‐square test) and improved granulation. This study summarises the clinical experiences derived from the evaluation of the sequential use concept in the daily clinical practice of wound treatment. On the basis of the wound healing results, patients' evaluation of treatment and the clinicians' and staff experiences, this concept was implemented at different Surgical Departments of the Charité‐Universitätsmedizin in Berlin.     

Care of chronic wounds in palliative care and end‐of‐life patients

The aim of this paper was to provide a literature synthesis on current wound care practices for the management of chronic wounds in palliative care and end‐of‐life patients, focusing on the control of wound‐related symptoms for comfort and improved quality of life. These wounds included pressure ulcers, venous and arterial leg ulcers, diabetic ulcers and fungating malignant wounds. Wound‐related symptoms included pain, exudate, malodour, infection, bleeding, dressing comfort and negative psychological and social functioning. Best care wound practices were formulated for each wound type to ease suffering based on the literature review. Although symptom management strategies for comfort may work in tandem with healing interventions, it is important to recognise when efforts towards wound closure may become unrealistic or burdensome for the patient at end of life. Thus, unique aspects of palliative wound care feature clinical indicators for early recognition of delayed healing, quality of life measurement tools related to chronic wounds, and comfort care strategies that align with patient wishes and realistic expectations for wound improvement.     

A prospective randomised open label study to evaluate the potential of a new silver alginate/carboxymethylcellulose antimicrobial wound dressing to promote wound healing

The aim of this study was to observe both the clinical signs and symptoms of wounds at risk of infection, that is critically colonised (biofilm infected) and antimicrobial‐performance of an ionic silver alginate/carboxymethylcellulose (SACMC) dressing, in comparison with a non silver calcium alginate fibre (AF) dressing, on chronic venous leg and pressure ulcers. Thirty‐six patients with venous or pressure ulcers, considered clinically to be critically colonised (biofilm infected), were randomly chosen to receive either an SACMC dressing or a non silver calcium AF dressing. The efficacy of each wound dressing was evaluated over a 4‐week period. The primary study endpoints were prevention of infection and progression to wound healing. The SACMC group showed a statistically significant (P = 0·017) improvement to healing as indicated by a reduction in the surface area of the wound, over the 4‐week study period, compared with AF controls. In conclusion, the SACMC dressing showed a greater ability to prevent wounds progressing to infection when compared with the AF control dressing. In addition, the results of this study also showed an improvement in wound healing for SACMC when compared with a non silver dressing.     

Biofilms in chronic wounds

Chronic wounds including diabetic foot ulcers, pressure ulcers, and venous leg ulcers are a worldwide health problem. It has been speculated that bacteria colonizing chronic wounds exist as highly persistent biofilm communities. This research examined chronic and acute wounds for biofilms and characterized microorganisms inhabiting these wounds. Chronic wound specimens were obtained from 77 subjects and acute wound specimens were obtained from 16 subjects. Culture data were collected using standard clinical techniques. Light and scanning electron microscopy techniques were used to analyze 50 of the chronic wound specimens and the 16 acute wound specimens. Molecular analyses were performed on the remaining 27 chronic wound specimens using denaturing gradient gel electrophoresis and sequence analysis. Of the 50 chronic wound specimens evaluated by microscopy, 30 were characterized as containing biofilm (60%), whereas only one of the 16 acute wound specimens was characterized as containing biofilm (6%). This was a statistically significant difference ( p <0.001). Molecular analyses of chronic wound specimens revealed diverse polymicrobial communities and the presence of bacteria, including strictly anaerobic bacteria, not revealed by culture. Bacterial biofilm prevalence in specimens from chronic wounds relative to acute wounds observed in this study provides evidence that biofilms may be abundant in chronic wounds.     

The specialized wound care center: a 7-year experience at a tertiary care hospital

Multidisciplinary wound care centers have proliferated as a result of an increasing need for care of nonhealing wounds. Information regarding types of wounds treated, length of treatment, compliance with treatment, and rates of healing was collected from a tertiary care hospital-based wound center over a 7-year period. Venous stasis ulcers were the most common type of wound treated (21%) and were also the most likely to heal. Pressure ulcers (20%), diabetic neuropathic ulcers (14%), ischemic ulcers (6%), and postsurgical wounds (6%) comprised the remainder of wounds treated. The success of treating wounds varied greatly with the wound's etiology. Despite the chronic nature of these wounds, most patients did not become long-term patients of the wound center. This study provides baseline outcome measures, which can serve as the basis for the comparison of treatment protocols and the development of prospective clinical trials.     

Evaluation of wound fluid biomarkers to determine healing in adults with venous leg ulcers: A prospective study

Clinical practice guidelines recommend using repeated wound surface area measurements to determine if a chronic ulcer is healing. This results in delays in determining the healing status. This study aimed to evaluate whether any of a panel of biomarkers can determine the healing status of chronic venous leg ulcers. Forty‐two patients with chronic venous leg ulcers had their wound measured and wound fluid collected at weekly time points for 13 weeks. Wound fluid was analyzed using multiplex enzyme‐linked immunosorbent assay to determine the concentration of biomarkers in the wound fluid at each weekly time point. Healing status was determined by examining the change in wound size at the previous and subsequent weeks. Predictive accuracy with 95% confidence intervals (CI) is reported. Of 42 patients, 105 evaluable weekly time points were obtained, with 32 classified as healing, 27 as nonhealing, and 46 as indeterminate. Thirteen biomarkers significantly differed between healing and nonhealing wounds (p < 0.1) and were included in a multivariate logistic regression model. Granulocyte macrophage‐colony stimulating factor (p < 0.001) and matrix metalloprotease‐13 (p = 0.004) were the best predictors of wound healing. Receiver operating characteristic curves indicated 92% accuracy (95% CI: 85%,100%) for granulocyte macrophage‐colony stimulating factor, and 78% accuracy (95% CI: 65%,90%) for matrix metalloprotease‐13 in discriminating between healing and nonhealing wounds. This study found that two biomarkers from wound fluid can predict healing status in chronic venous leg ulcers. These findings may lead to the ability to determine the future trajectory of a wound and the ability to modify treatment accordingly.     

A study on the ability of quaternary ammonium groups attached to a polyurethane foam wound dressing to inhibit bacterial attachment and biofilm formation

Bacterial infection of acute and chronic wounds impedes wound healing significantly. Part of this impediment is the ability of bacterial pathogens to grow in wound dressings. In this study, we examined the effectiveness of a polyurethane (PU) foam wound dressings coated with poly diallyl‐dimethylammonium chloride (pDADMAC‐PU) to inhibit the growth and biofilm development by three main wound pathogens, Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii, within the wound dressing. pDADMAC‐PU inhibited the growth of all three pathogens. Time‐kill curves were conducted both with and without serum to determine the killing kinetic of pDADMAC‐PU. pDADMAC‐PU killed S. aureus, A. baumannii, and P. aeruginosa. The effect of pDADMAC‐PU on biofilm development was analyzed quantitatively and qualitatively. Quantitative analysis, colony‐forming unit assay, revealed that pDADMAC‐PU dressing produced more than eight log reduction in biofilm formation by each pathogen. Visualization of the biofilms by either confocal laser scanning microscopy or scanning electron microscopy confirmed these findings. In addition, it was found that the pDADMAC‐PU‐treated foam totally inhibited migration of bacteria through the foam for all three bacterial strains. These results suggest that pDADMAC‐PU is an effective wound dressing that inhibits the growth of wound pathogens both within the wound and in the wound dressing.     

Does localized iron loss in venous disease lead to systemic iron deficiency? A descriptive pilot study

Haemosiderin deposition in the legs of patients with venous leg ulcers is well established, and several theories suggest this stored iron has a role in disease pathophysiology. In this novel pilot study of patients with chronic venous leg ulcers, we aimed to establish the relationship between wound fluid iron levels, serum iron parameters and healing. Fifteen patients with venous ulcers were included in the study. Blood samples were taken for full blood count and iron studies, while simultaneously wound fluid was obtained from the wound surface using filter paper. Wound areas were measured at initial and 4 week (+/? 2 day) follow‐up visits. We found a positive correlation between wound fluid and serum iron (correlation co‐efficient 0.27) and those with the lowest wound fluid iron level were also anemic. No association was found between initial wound area and wound fluid iron level but the largest wound areas were found in patients with anemia. Only 38% of patients demonstrated a reduction in wound area during the 4 week study, and 80% of those were not anemic or iron deficient. Conversely in those patients whose wounds did not reduce in size 88% were anemic or iron deficient. These findings demonstrate a previously unrecognized phenomenon of systemic iron store depletion secondary to leaching out of the body in wound exudate. In addition, these results suggest a high prevalence of anemia in patients with chronic venous ulcers, though whether this is cause or effect requires further research. Our findings also suggest that patients with venous ulcers have a high prevalence of iron deficiency and anemia, which appears to be often undiagnosed, and that diagnostic criteria for iron deficiency in patients with chronic wounds need to be revised to reflect the effect of chronic inflammation on iron metabolism.     

Improving the quality of pressure ulcer management in a skilled nursing facility

Pressure ulcers (PUs) are a serious health care problem for nursing home residents and a key quality metric for regulators. Three initiatives were introduced at a 128‐bed facility to improve PU prevention. First, a Quality Assurance and Performance Improvement project and a Root Cause Analysis were conducted to improve the facility's wound care programme. Second, a digital wound care management solution was adopted to track wound management. Third, the role of skin integrity coordinator was created as a central point of accountability for wound care‐related activities and related performance metrics. Improvements in PU prevention were tracked using Centers of Medicare and Medicaid data, specifically (a) the percentage of long‐stay high‐risk residents with PUs and (b) the percentage of short‐stay residents with PUs that are new or have worsened. PU prevalence for long‐stay high‐risk residents was 12.99% (Q4 2016), and upon implementation of these initiatives, the facility saw continued reductions in PU prevalence to 2.9% (Q4 2017), while PUs for short‐stay residents were maintained at zero throughout this period. This study highlights the power of effective management combined with real‐time data analytics, as enabled by digital wound care management, to make significant improvements in health care delivery.     

Maggot versus conservative debridement therapy for the treatment of pressure ulcers

To define the efficacy and safety of maggot therapy, a cohort of 103 inpatients with 145 pressure ulcers was evaluated. Sixty-one ulcers in 50 patients received maggot therapy at some point during their monitored course; 84 ulcers in 70 patients did not. Debridement and wound healing could be quantified for 43 maggot-treated wounds and 49 conventionally treated wounds. Eighty percent of maggot-treated wounds were completely debrided, while only 48% of wounds were completely debrided with conventional therapy alone (p=0.021). Within 3 weeks, maggot-treated wounds contained one-third the necrotic tissue (p = 0.05) and twice the granulation tissue (p < 0.001), compared to non-maggot-treated wounds. Of the 31 measurable maggot-treated wounds monitored initially during conventional therapy, necrotic tissue decreased 0.2 cm(2) per week during conventional therapy, while total wound area increased 1.2 cm(2) per week. During maggot therapy, necrotic tissue decreased 0.8 cm(2) per week (p = 0.003) and total wound surface area decreased 1.2 cm2 per week (p = 0.001). Maggot therapy was more effective and efficient in debriding chronic pressure ulcers than were the conventional treatments prescribed. Patients readily accepted maggot therapy, and adverse events were uncommon.     

An open multicenter comparative randomized clinical study on chitosan

Chitosan, a natural polysaccharide derivate from chitin, offers a promising alternative biomaterial for use in wound dressings. In this work, the safety and efficacy of a next‐generation KA01 chitosan wound dressing in facilitating the healing of nonhealing chronic wounds was studied. This open multicenter comparative prospective randomized clinical study was conducted at three medical centers in China. A total of 90 patients (45 in test group and 45 in control group) with unhealed chronic wounds including pressure ulcers, vascular ulcers, diabetic foot ulcers, and wounds with minor infections, or at risk of infection, were treated with the next generation chitosan wound dressing as the test article or traditional vaseline gauze as a control. Baseline assessments were undertaken with the primary end point being wound area reduction. The secondary end points included pain reduction (using the NRS11 pain scale) at dressing change, wound exudate levels, wound depth and duration of the treatment. After 4 weeks treatment, the wound area reduction was significantly greater in the test group (65.97 ± 4.48%) than the control group (39.95 ± 4.48%). The average pain level in the test group was 1.12 ± 0.23 and 2.30 ± 0.23 in the control group. The wound depth was also lower in the test group 0.30 ± 0.48 cm than the control group 0.54 ± 0.86 cm. The level of exudate fell and the dressing could be removed integrally in both the test and control groups. The mean duration of the test group was 27.31 ± 5.37 days and control group 27.09 ± 6.44 days. No adverse events were reported in either group. In conclusion this open multicenter comparative prospective randomized clinical study has provided compelling evidence that the next generation chitosan wound dressing can enhance wound progression towards healing by facilitating wound reepithelialization and reducing the patients pain level. Furthermore the dressing was shown to be clinically safe and effective in the management of chronic wounds.     

Extracellular matrix assessment of infected chronic venous leg ulcers: role of metalloproteinases and inflammatory cytokines

Chronic venous ulcer (CVU) represents a dreaded complication of chronic venous disease (CVD). The onset of infection may further delay the already precarious healing process in such lesions. Some evidences have shown that matrix metalloproteinases (MMPs) are involved and play a central role in both CVUs and infectious diseases. Two groups of patients were enrolled to evaluate the expression of MMPs in infected ulcers and the levels of inflammatory cytokines as well as their prevalence. Group I comprised 63 patients (36 females and 27 males with a median age of 68·7 years) with infected CVUs, and group II (control group) comprised 66 patients (38 females and 28 males with a median age of 61·2 years) with non‐infected venous ulcers. MMP evaluation and dosage of inflammatory cytokines in plasma and wound fluid was performed by means of enzyme‐linked immunosorbent assay test; protein extraction and immunoblot analysis were performed on biopsied wounds. The first three most common agents involved in CVUs were Staphylococcus aureus (38·09%), Corynebacterium striatum (19·05%) and Pseudomonas aeruginosa (12·7%). In this study, we documented overall higher levels of MMP‐1 and MMP‐8 in patients with infected ulcers compared to those with uninfected ulcers that showed higher levels of MMP‐2 and MMP‐9. We also documented higher levels of interleukin (IL)‐1, IL‐6, IL‐8, vascular endothelial growth factor and tumour necrosis factor‐alpha in patients with infected ulcers with respect to those with uninfected ulcers, documenting a possible association between infection, MMP activation, cytokine secretions and symptoms. The present results could represent the basis for further studies on drug use that mimic the action of tissue inhibitors of metalloproteinases in order to make infected CVU more manageable.     

Effectiveness of biofilm‐based wound care system on wound healing in chronic wounds

A biofilm plays a crucial role in delaying wound healing. Sharp debridement, a possible effective method for eliminating biofilms, can only be applied to the wound with visible necrotic tissue; thus, no option has been available for eliminating biofilms that are not accompanied by necrotic tissue. Wound blotting was recently developed to visualize biofilm noninvasively and quickly, and ultrasonic debridement is available for biofilm removal. Therefore, the purpose of this study was to investigate the efficacy of “biofilm‐based wound care system (BWCS),” a combination of wound blotting as a point‐of‐care testing and ultrasonic debridement, for promoting wound healing. Firstly, the cross‐sectional study was conducted to examine the proportion of biofilm removal by ultrasonic debridement in pressure ulcers [Study 1]. Subsequently, the retrospective cohort study was conducted to examine the effectiveness of BWCS for healing of chronic wounds [Study 2]. The proportions of wound healing between wounds treated with BWCS and those with standard care in the home‐visiting clinic were compared by Kaplan–Meier curve, and the Cox proportional hazard modeling was used to assess the effect of BWCS on wound healing. In Study 1, the median of biofilm removal proportion was 38.9% (interquartile range, 12.9–68.0%) for pressure ulcers treated with standard care and 65.2% (41.1–78.8%) for those treated with ultrasonic debridement (p = 0.009). In Study 2, the proportion of wound healing within 90 days was significantly higher in wounds treated with BWCS than in those treated with standard care (p = 0.001). The adjusted hazard ratio of BWCS for wound healing was 4.5 (95% confidence interval, 1.3–15.0; p = 0.015). In conclusion, we demonstrated that our novel approach, BWCS, can be a promising therapeutic strategy for visualizing biofilms that are not accompanied by necrotic tissue and promoting healing in chronic wounds.     

Coverage of the infected wound.

Fifty-four consecutive patients with chronic wounds were identified by the following criteria: (1) established infection for 6 months, (2) exposure of bone, mediastinum, or other vital structure, (3) mechanical and/or vascular limitations to delayed closure techniques, (4) no response to wound debridement in prolonged antibiotic therapy. These wounds were divided into four groups: osteomyelitis (21), pressure sore (17), soft tissue wound (10), and osteoradionecrosis (6). Wound treatment in all patients included debridement, muscle flap closure, and culture specific antibiotic therapy. These consecutively treated patients over a 4-year period presented with an average duration of chronic infection of 2.9 years. Ninety-three per cent of these patients after treatment have demonstrated stable coverage without recurrent infection with a minimum of 1 year and a maximum of 4.6 years follow-up. The results demonstrate safe, effective coverage (93% of patients) of chronic infected wounds associated with long bone and pelvic osteomyelitis as well as chronic perineal sinuses following proctocolectomy and osteoradionecrosis. Debridement with short-term (average 12 days) antibiotic therapy has been effective when muscle flap coverage is provided.     

The diagnosis of infection in chronic leg ulcers: A narrative review on clinical practice

This literature review aimed to provide a narrative review of evidence on validity of clinical and microbial indicators of infection and to gain insights into the diagnosis of infection in chronic leg ulcers (CLUs). A search was conducted in Cinahl, Medline, the Cochrane Library databases, Embase, Web of Science, ScienceDirect, Pubmed, PsycINFO, ProQuest dissertations, and Google Scholar from January 1990 to July 2017. The inclusion criteria were original studies, systematic reviews, and consensus documents focused on “infection” in CLUs, English language, clinical and community settings, and human. The reviewed studies were inconsistent in criteria for infection between investigated wound types and lack of specificity regarding wound types. There were few studies investigating the criteria for diagnosis of infection in leg ulcers. The identification of leg ulcer infection still remains problematic and relies on out‐of‐date and not uniform evidence. Literature in this area was mostly limited to level III and IV evidence based on The Australian National Health and Medical Research Council Levels of Evidence, or expert opinion. This literature review showed seven clinical signs and symptoms that could be diagnostic for infection in CLUs, including: new, increased, or altered ulcer pain; malodour; increased ulcer area; wound breakdown, delayed or non‐healing; and erythema and increased local temperature, whilst the microbial indicators used to diagnose infected leg ulcers were varied and regarded as less important.